CCR7-mediated T follicular helper cell differentiation is associated with the pathogenesis and immune microenvironment of spinal cord injury-induced immune deficiency syndrome.
CCR7-mediated T follicular helper cell differentiation is associated with the pathogenesis and immune microenvironment of spinal cord injury-induced immune deficiency syndrome.
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DOI：
10.3389/fnins.2022.1019406
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发表时间：
2022
影响因子：
4.3
通讯作者：
Cui, Zhiming
中科院分区：
文献类型：
--
作者：
Li, Chaochen;Wu, Chunshuai;Xu, Guanhua;Liu, Yang;Chen, Jiajia;Zhang, Jinlong;Hong, Hongxiang;Ji, Chunyan;Cui, Zhiming
关键词：
脊髓损伤诱导的免疫缺陷综合征（SCI-IDS）是一种以继发于SCI的全身性免疫抑制为特征的疾病，其显著增加了感染的可能性并且难以治疗。本研究探讨了CCR 7在SCI-IDS发生和免疫微环境组成中的作用。从基因表达综合数据库收集来自SCI和非SCI受试者的外周血白细胞的基因表达谱数据。根据差异基因表达分析、蛋白质-蛋白质相互作用（PPI）网络和风险模型构建，CCR 7表达水平与急性SCI显著相关，并且CCR 7表达在急性SCI后显著下调。接下来，我们构建了一个临床预测模型，并用它来识别急性SCI患者。利用基因本体（GO）分析和基因集富集分析（GSEA），我们发现急性脊髓损伤后免疫相关的生物学过程，如T细胞受体信号通路被抑制，而趋化因子相关的信号通路被激活。使用单一样品GSEA和CIBERSORT进行的免疫浸润分析表明，Tfh细胞功能与CCR 7表达水平显著相关，并且在急性SCI后显著降低。急性脊髓损伤分为两个亚型，我们整合多个分类器来分析和阐明两个亚型的免疫调节关系。结果表明，CCR 7通过激活Tfh细胞中的趋化因子信号通路来抑制免疫缺陷表型。总之，CCR 7表现出作为急性SCI的诊断标志物的潜力。
Spinal cord injury-induced immune deficiency syndrome (SCI-IDS) is a disorder characterized by systemic immunosuppression secondary to SCI that dramatically increases the likelihood of infection and is difficult to treat. T follicular helper (Tfh) cells regulated by chemokine receptor CCR7 are associated with SCI-IDS after acute SCI. The present study explored the roles of CCR7 in SCI-IDS occurrence and immune microenvironment composition. Gene expression profile data of peripheral blood leukocytes from SCI and non-SCI subjects were collected from the Gene Expression Omnibus database. According to differential gene expression analysis, a protein-protein interaction (PPI) network, and risk model construction, the CCR7 expression level was prominently related to acute SCI and CCR7 expression was significantly downregulated after acute SCI. Next, we constructed a clinical prediction model and used it to identify patients with acute SCI. Using Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA), we discovered that immune-related biological processes, such as T cell receptor signaling pathway, were suppressed, whereas chemokine-related signaling pathways were activated after acute SCI. Immune infiltration analysis performed using single sample GSEA and CIBERSORT suggested that Tfh cell function was significantly correlated with the CCR7 expression levels and was considerably reduced after acute SCI. Acute SCI was divided into two subtypes, and we integrated multiple classifiers to analyze and elucidate the immunomodulatory relationships in both subtypes jointly. The results suggested that CCR7 suppresses the immunodeficiency phenotype by activating the chemokine signaling pathway in Tfh cells. In conclusion, CCR7 exhibits potential as a diagnostic marker for acute SCI.
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影响因子：
16.6
作者：
Carpenter, Randall S.;Marbourg, Jessica M.;Popovich, Phillip G.
通讯作者：
Popovich, Phillip G.
影响因子：
3
作者：
Galeiras Vazquez, R.;Ferreiro Velasco, M. E.;Salvador de la Barrera, S.
通讯作者：
Salvador de la Barrera, S.
影响因子：
5.4
作者：
Arnold, Carrie N.;Campbell, Daniel J.;Butcher, Eugene C.
通讯作者：
Butcher, Eugene C.
影响因子：
4.7
作者：
Li, Wenli;Wang, Huimei;Liu, Jun
通讯作者：
Liu, Jun
DOI：
10.1038/sc.1996.14
发表时间：
1996-02-01
期刊：
PARAPLEGIA
影响因子：
--
作者：
Kliesch, WF;Cruse, JM;Lampton, JA
通讯作者：
Lampton, JA